The Janus kinases–signal transducers and activators of transcription (JAK-STAT) signalling pathway are a pleiotropic cascade that involves ligands such as cytokines, hormones, and growth factors. Among cytokines, interleukin (IL)-17, IL-22, IL-23, and tumour necrosis factor (TNF)-alpha play a pivotal role in psoriasis. We aimed at investigating in an organotypic experimental model of normal human skin (n = 7 women between 20–40 years old, non-smokers) the early, direct, and specific effects of IL-17, IL-22, IL-23, TNF-alpha and a combination of the four cytokines (Mix) on the JAK-STAT/pathway. The expression of the psoriatic marker keratin (K) 17 was analyzed by immunofluorescence and molecular techniques after exposure to IL-23 or Mix. The Mix elicited a strong K17 up-regulation in keratinocytes at 72 h, reinforcing the hypothesis of a synergistic effect of different cytokines. High levels of JAK1 and STAT3 activation were detected, suggesting the involvement of JAK1/STAT3 pathway in the upregulation of K17. As the present study in an organotypic model of human skin reports a variable expression of JAK-STAT upon different cytokine stimuli and most of the JAK inhibitors for the psoriasis treatment have proven to have a clinical efficacy, these observations have a relevance to better understand the mechanisms of JAK-inhibitors in the skin.

Inside-out and outside-in organotypic normal human skin culture : JAK-STAT pathway is activated after pro-inflammatory psoriatic cytokine exposure / L. Cornaghi, N. Gagliano, F.W.B. Preis, F. Prignano, E. Donetti. - In: TISSUE & CELL. - ISSN 0040-8166. - 74(2022 Feb), pp. 101675.1-101675.6. [10.1016/j.tice.2021.101675]

Inside-out and outside-in organotypic normal human skin culture : JAK-STAT pathway is activated after pro-inflammatory psoriatic cytokine exposure

L. Cornaghi
Co-primo
;
N. Gagliano
Co-primo
;
E. Donetti
Ultimo
2022

Abstract

The Janus kinases–signal transducers and activators of transcription (JAK-STAT) signalling pathway are a pleiotropic cascade that involves ligands such as cytokines, hormones, and growth factors. Among cytokines, interleukin (IL)-17, IL-22, IL-23, and tumour necrosis factor (TNF)-alpha play a pivotal role in psoriasis. We aimed at investigating in an organotypic experimental model of normal human skin (n = 7 women between 20–40 years old, non-smokers) the early, direct, and specific effects of IL-17, IL-22, IL-23, TNF-alpha and a combination of the four cytokines (Mix) on the JAK-STAT/pathway. The expression of the psoriatic marker keratin (K) 17 was analyzed by immunofluorescence and molecular techniques after exposure to IL-23 or Mix. The Mix elicited a strong K17 up-regulation in keratinocytes at 72 h, reinforcing the hypothesis of a synergistic effect of different cytokines. High levels of JAK1 and STAT3 activation were detected, suggesting the involvement of JAK1/STAT3 pathway in the upregulation of K17. As the present study in an organotypic model of human skin reports a variable expression of JAK-STAT upon different cytokine stimuli and most of the JAK inhibitors for the psoriasis treatment have proven to have a clinical efficacy, these observations have a relevance to better understand the mechanisms of JAK-inhibitors in the skin.
Epidermis; JAK-STAT; Keratin 17; Psoriasis
Settore BIO/16 - Anatomia Umana
9-nov-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0040816621001919-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 4.53 MB
Formato Adobe PDF
4.53 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/886553
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 1
social impact